The present invention relates to novel cyclic compounds having antifungal activity (hereinafter referred to as Aerothricins), the use of Aerothricins in the medical therapy, pharmaceutical compositions containing Aerothricins as well as to processes for the preparation of Aerothricins.
Azole antifungal agents are currently widely used for the treatment of systemic mycoses. However, long term prophylactic use of azole antifungals resulted in generation of azole resistant Candida spp. due to their fungistatic action. Therefore, fungicidal agents are particularly important for treatment of severe systemic mycoses, especially against pulmonary aspergillosis. Furthermore, the currently available antifungal agents are not effective against Scedosporium spp. which is one of the emerging pathogens among immunocompromised patients. Amphotericin B is a highly effective fungicidal agent currently used clinically, but its therapeutic index (effective dose vs. toxic dose) is rather narrow. Certain cyclic compounds such as LY303366 (EP 736 541), WF11243 (EP 584 360) are known to show fungicidal activity through inhibition of β-1,3-glucan synthase. However, they have still some disadvantages in terms of antifungal spectrum and/or safety profile. Thus, development of new fungicidal agents with better safety profile and efficacy against major systemic pathogens including Aspergillus fumigatus and Scedosporium spp. is urgently required.